A new potential treatment for Retinitis Pigmentosa & Macular Degeneration

A team of researchers from the University of California, Berkeley, in collaboration with researchers at University of Munich and University of Washington in Seattle have found a chemical that can temporarily restore some amount of vision in blind mice.

This compound could eventually help those with Retinitis Pigmentosa, a common genetic disease that leads to blindness, as well as Age-related Macular Degeneration.

The chemical, referred to as AAQ, acts on the remaining cells in the retina, which are normally "blind" cells, sensitive to light. AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells; when switched on by light, it alters the flow of ions through the channels and activates these neurons similar to the way rods and cones are activated by light.

This chemical has been shown to eventually wear off, and hence may offer a safer alternative to other approaches that restore sight, such as gene or stem cell therapies, which may permanently change the retina. It is also less invasive than implanting light-sensitive chips in the eye.

Considering that it is a simple chemical, it will be easy to change the dosage, use it in combination with other therapies, or discontinue the therapy if the need be. This would allow new and improved chemicals that may become available in time to be offered to the same patients.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, the researchers confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light. The mice also demonstrated light avoidance, a typical rodent behavior impossible without the animals being able to see some light. The researchers are hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

It will be a while before this compound will find its way in humans. The researchers have to show that these compounds are safe and will work in patients the way they work in mice. BUt these preliminary results demonstrate that this class of compound restores light sensitivity to retinas blind from genetic disease.

The current technologies being evaluated for restoring sight to people whose rods and cones have died include injection of stem cells to regenerate the rods and cones; "optogenetics," a type of gene therapy where a photoreceptor gene is inserted into blind neurons to make them sensitive to light; and installation of electronic prosthetic devices, such as a small light-sensitive retinal chip with electrodes that stimulate blind neurons.

Eight years ago, Kramer, Trauner, a former UC Berkeley chemist now at the University of Munich, and their colleagues developed an optogenetic technique to chemically alter potassium ion channels in blind neurons so that a photoswitch could latch on. Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons.

Subsequently, Trauner synthesized AAQ (acrylamide-azobenzene-quaternary ammonium), a photoswitch that attaches to potassium channels without the need to genetically modify the channel.

Newer versions of AAQ now being tested have demonstrated better results, as per the researchers. They activate neurons for days rather than hours using blue-green light of moderate intensity, and these photoswitches naturally deactivate in darkness, so that a second color of light is not needed to switch them off.

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